Diagnosis and Management of Exit Site Infection in Peritoneal Dialysis Patients

Exit site infection (ESI) is an important clinical problem in peritoneal dialysis (PD) patients and is a significant cause of peritonitis and catheter loss. While most ESIs are caused by skin commensals, rising incidence of atypical and resilient organisms such as mycobacteria, Pseudomonas and Burkholderia species has been observed. The diagnosis and management of these emerging pathogen remain difficult and poorly defined. This chapter highlights the evaluation and management of ESI in PD patients. The clinical features, microbiology, and ultrasonographic findings are discussed. The general and specific management of ESI due to different organisms will also be elaborated. ESI is usually a clinical diagnosis, but the use of bedside ultrasound can help assess for any collection around the cuff and tunnel tract involvement. Topical prophylaxis remains an effective way to prevent ESI. While the majority ESIs are related to skin flora and can be managed successfully by topical or systemic antimicrobials, clinicians should be alert to the emergence of resistant and atypical microorganisms. Surgical treatment should be reserved for ESI refractory to medical treatment or those with associated peritonitis

Adjuvant Therapies in Colon Cancer

Most of the patients with localized colon cancer undergo curative resection. However, significant number of patients will recur with metastatic disease, especially those with node positive cancer. Adjuvant chemotherapy has shown to improve cure rate and survival by eradicating micrometastases. The benefit of adjuvant therapy is well established in node-positive cancers, while their role in stage II cancer is not well defined. A number of molecular markers have been identified that are prognostic and/or predictive in colon cancer. Such molecular markers, and other clinicopathological features play an important role in selection of appropriate therapy and duration of treatment. Emerging evidence for the utility of genomic profiling or detection of circulating tumor DNA (ctDNA) are promising which may further facilitate decision making in the future. This chapter reviews the evolution of adjuvant therapy for resected colon cancer, the current evidence and the factors influence the choice of therapy

Consumers’ Adoption of B2C E-Commerce in Macao

This research sets out to determine factors that influence consumers’ adoption of B2C E-commerce in Macao. While prior research has shown that there are many factors that influence E-commerce adoption, this research hypothesized that two variables – namely, trust and willingness to use credit cards for online transactions – influence E-commerce adoption in Macao. This research further hypothesized that trust and willingness to use credit card interact to influence adoption. Using data collected from a questionnaire survey, the results of this study found that the two hypothesized variables are positively related to intention to adopt E-commerce. The results also support the interaction effect. The nature of interaction showed that trust is related to E-commerce adoption only when willingness to use credit card for online transaction is high. Also, willingness to use credit card for online transaction is related to E-commerce adoption only when the level of trust is high. These results provide a richer understanding of the relationship between the hypothesized variables and Ecommerce adoption. This study also collected interview data related to Internet users’ adoption of E-commerce. The interview data provide a better understanding on why Macao people are afraid of using credit card for online transactions. The researchers gathered more information about interviewees’ credit card usage and habits, their attitudes toward credit card security, and their thoughts regarding identity theft. The interviews also uncovered other factors that may influence E-commerce adoption

Universal molecular screening does not effectively detect Lynch syndrome in clinical practice

Background: Lynch syndrome (LS) due to an inherited damaging mutation in mismatch repair (MMR) genes comprises 3% of all incident colorectal cancer (CRC). Molecular testing using immunohistochemistry (IHC) for MMR proteins is a recommended screening tool to identify LS in incident CRC. This study assessed outcomes of population-based routine molecular screening for diagnosis of LS in a regional center. Methods: We conducted a prospective, consecutive case series study of universal IHC testing on cases of resected CRC from September 2004–December 2013. Referred cases with abnormal IHC results that attended a familial cancer clinic were assessed according to modified Bethesda criteria (until 2009) or molecular criteria (from 2009). Results: 1612 individuals underwent resection for CRC in the study period and had MMR testing by IHC. Of these, 274 cases (16.9%) exhibited loss of expression of MMR genes. The mean age at CRC diagnosis was 68.1 years (± standard deviation 12.7) and the mean age of those with an IHC abnormality was 71.6 (± 11.8). A total of 82 (29.9%) patients with an abnormal result were seen in a subspecialty familial cancer clinic. Patients aged under 50 (p = 0.009) and those with loss of MSH6 staining (p = 0.027) were more likely to be referred and to attend. After germ-line sequencing, 0.6% (10 of 82) were identified as having a clinically significant abnormality. A further eight probands with pathogenic germ-line mutations were identified from other referrals to the service over the same time period. Conclusions: While technically accurate, the yield of ‘universal’ IHC in detecting new Lynch probands is limited by real-world factors that reduce referrals and genetic testing. We propose an alternative approach for universal, incident case detection of Lynch syndrome with ‘one-stop’ MMR testing and sequencing.This work was supported by a grant from the Canberra Hospital Private Practice Fund (to DT)

Models for predicting venous thromboembolism in ambulatory patients with lung cancer:A systematic review and meta-analysis

AimsThe incidence of venous thromboembolism (VTE) in patients with lung cancer is relatively high, and risk stratification models are vital for the targeted application of thromboprophylaxis. We aimed to review VTE risk prediction models that have been developed in patients with lung cancer and evaluate their performance.Methods and resultsTwenty-four eligible studies involving 123,493 patients were included. The pooled incidence of VTE within 12 months was 11 % (95 % CI 8 %–14 %). With the identified four existing VTE risk assessment tools, meta-analyses did not show a significant discriminatory capability of stratifying VTE risk using Khorana, PROTECHT and CONKO scores. The pooled sensitivity and specificity of the Khorana score were 24 % (95 % CI 11 %–44 %) and 84 % (95 % CI 73 %–91 %) at the 3-point cut-off, and 43 % (95 % CI 35 %–52 %) and 61 % (95 % CI 52 %–69 %) at the 2-point cut-off. A COMPASS-CAT score ≥ 7 points indicated a significantly high VTE risk, with a RR of 4.68 (95 % CI 1.05–20.80).ConclusionsThe Khorana score lacked discriminatory capability in identifying patients with lung cancer at high VTE risk, regardless of the cut-off value. The COMPASS-CAT score had better performance, but further validation is needed. The results indicate the need for robust VTE risk assessment tools specifically designed and validated for lung cancer patients. Future research should include relevant biomarkers as important predictors and consider the combined use of risk tools.PROSPERO registration number: CRD42021245907

Optimizing poly (ADP-ribose) polymerase inhibition through combined epigenetic and immunotherapy

Triple‐negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor survival outcomes. Currently, there are no targeted therapies available for TNBCs despite remarkable progress in targeted and immune‐directed therapies for other solid organ malignancies. Poly (ADP‐ribose) polymerase inhibitors (PARPi) are effective anticancer drugs that produce good initial clinical responses, especially in homologous recombination DNA repair‐deficient cancers. However, resistance is the rule rather than the exception, and recurrent tumors tend to have an aggressive phenotype associated with poor survival. Many efforts have been made to overcome PARPi resistance, mostly by targeting genes and effector proteins participating in homologous recombination that are overexpressed during PARPi therapy. Due to many known and unknown compensatory pathways, genes, and effector proteins, overlap and shared resistance are common. Overexpression of programmed cell death‐ligand 1 (PD‐L1) and cancer stem cell (CSC) sparing are novel PARPi resistance hypotheses. Although adding programmed cell death‐1 (PD‐1)/PD‐L1 inhibitors to PARPi might improve immunogenic cell death and be crucial for durable responses, they are less likely to target the CSC population that drives recurrent tumor growth. Lysine‐specific histone demethylase‐1A and histone deacetylase inhibitors have shown promising activity against CSCs. Combining epigenetic drugs such as lysine‐specific histone demethylase‐1A inhibitors or histone deacetylase inhibitors with PARPi/anti‐PD‐1/PD‐L1 is a novel, potentially synergistic strategy for priming tumors and overcoming resistance. Furthermore, such an approach could pave the way for the identification of new upstream epigenetic and genetic signatures.This work was supported by the National Health and Medical Research Council (Grant ID APP1068065) and the UC Deepwater Scholarship (TP)

A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy

BACKGROUND: To prospectively evaluate the efficacy and safety of selective internal radiation (SIR) spheres in patients with inoperable liver metastases from colorectal cancer who have failed 5FU based chemotherapy. METHODS: Patients were prospectively enrolled at three Australian centres. All patients had previously received 5-FU based chemotherapy for metastatic colorectal cancer. Patients were ECOG 0–2 and had liver dominant or liver only disease. Concurrent 5-FU was given at investigator discretion. RESULTS: Thirty patients were treated between January 2002 and March 2004. As of July 2004 the median follow-up is 18.3 months. Median patient age was 61.7 years (range 36 – 77). Twenty-nine patients are evaluable for toxicity and response. There were 10 partial responses (33%), with the median duration of response being 8.3 months (range 2–18) and median time to progression of 5.3 mths. Response rates were lower (21%) and progression free survival shorter (3.9 mths) in patients that had received all standard chemotherapy options (n = 14). No responses were seen in patients with a poor performance status (n = 3) or extrahepatic disease (n = 6). Overall treatment related toxicity was acceptable, however significant late toxicity included 4 cases of gastric ulceration. CONCLUSION: In patients with metastatic colorectal cancer that have previously received treatment with 5-FU based chemotherapy, treatment with SIR-spheres has demonstrated encouraging activity. Further studies are required to better define the subsets of patients most likely to respond

Chemotherapy and radiotherapy for advanced pancreatic cancer

Background: Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review attempts to synthesise all the randomised data available to help better inform patient and clinician decision-making when dealing with this difficult disease. Objectives: To assess the effect of chemotherapy, radiotherapy or both for first-line treatment of advanced pancreatic cancer. Our primary outcome was overall survival, while secondary outcomes include progression-free survival, grade 3/4 adverse events, therapy response and quality of life. Search methods: We searched for published and unpublished studies in CENTRAL (searched 14 June 2017), Embase (1980 to 14 June 2017), MEDLINE (1946 to 14 June 2017) and CANCERLIT (1999 to 2002) databases. We also handsearched all relevant conference abstracts published up until 14 June 2017. Selection criteria: All randomised studies assessing overall survival outcomes in patients with advanced pancreatic ductal adenocarcinoma. Chemotherapy and radiotherapy, alone or in combination, were the eligible treatments. Data collection and analysis: Two review authors independently analysed studies, and a third settled any disputes. We extracted data on overall survival (OS), progression-free survival (PFS), response rates, adverse events (AEs) and quality of life (QoL), and we assessed risk of bias for each study. Main results: We included 42 studies addressing chemotherapy in 9463 patients with advanced pancreatic cancer. We did not identify any eligible studies on radiotherapy. We did not find any benefit for chemotherapy over best supportive care. However, two identified studies did not have sufficient data to be included in the analysis, and many of the chemotherapy regimens studied were outdated. Compared to gemcitabine alone, participants receiving 5FU had worse OS (HR 1.69, 95% CI 1.26 to 2.27, moderate-quality evidence), PFS (HR 1.47, 95% CI 1.12 to 1.92) and QoL. On the other hand, two studies showed FOLFIRINOX was better than gemcitabine for OS (HR 0.51 95% CI 0.43 to 0.60, moderate-quality evidence), PFS (HR 0.46, 95% CI 0.38 to 0.57) and response rates (RR 3.38, 95% CI 2.01 to 5.65), but it increased the rate of side effects. The studies evaluating CO-101, ZD9331 and exatecan did not show benefit or harm when compared with gemcitabine alone. Giving gemcitabine at a fixed dose rate improved OS (HR 0.79, 95% CI 0.66 to 0.94, high-quality evidence) but increased the rate of side effects when compared with bolus dosing. When comparing gemcitabine combinations to gemcitabine alone, gemcitabine plus platinum improved PFS (HR 0.80, 95% CI 0.68 to 0.95) and response rates (RR 1.48, 95% CI 1.11 to 1.98) but not OS (HR 0.94, 95% CI 0.81 to 1.08, low-quality evidence). The rate of side effects increased. Gemcitabine plus fluoropyrimidine improved OS (HR 0.88, 95% CI 0.81 to 0.95), PFS (HR 0.79, 95% CI 0.72 to 0.87) and response rates (RR 1.78, 95% CI 1.29 to 2.47, high-quality evidence), but it also increased side effects. Gemcitabine plus topoisomerase inhibitor did not improve survival outcomes but did increase toxicity. One study demonstrated that gemcitabine plus nab-paclitaxel improved OS (HR 0.72, 95% CI 0.62 to 0.84, high-quality evidence), PFS (HR 0.69, 95% CI 0.58 to 0.82) and response rates (RR 3.29, 95% CI 2.24 to 4.84) but increased side effects. Gemcitabine-containing multi-drug combinations (GEMOXEL or cisplatin/epirubicin/5FU/gemcitabine) improved OS (HR 0.55, 95% CI 0.39 to 0.79, low-quality evidence), PFS (HR 0.43, 95% CI 0.30 to 0.62) and QOL. We did not find any survival advantages when comparing 5FU combinations to 5FU alone. Authors' conclusions: Combination chemotherapy has recently overtaken the long-standing gemcitabine as the standard of care. FOLFIRINOX and gemcitabine plus nab-paclitaxel are highly efficacious, but our analysis shows that other combination regimens also offer a benefit. Selection of the most appropriate chemotherapy for individual patients still remains difficult, with clinicopathological stratification remaining elusive. Biomarker development is essential to help rationalise treatment selection for patients